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Download fileFungal Highly Reducing Polyketide Synthases Biosynthesize Salicylaldehydes That Are Precursors to Epoxycyclohexenol Natural Products
journal contribution
posted on 05.12.2019, 19:58 authored by Ling Liu, Man-Cheng Tang, Yi TangFungal highly reducing polyketide synthases (HRPKSs)
are highly
programmed multidomain enzymes that synthesize reduced polyketide
structures. Recent reports indicated salicylaldehydes are synthesized
by HRPKS biosynthetic gene clusters, which are unexpected based on
known enzymology of HRPKSs. Using genome mining of a Trichoderma
virens HRPKS gene cluster that encodes a number of redox
enzymes, we uncover the strategy used by HRPKS pathways in the biosynthesis
of aromatic products such as salicylaldehyde 4, which
can be oxidatively modified to the epoxycyclohexanol natural product
trichoxide 1. We show selective β-hydroxyl groups
in the linear HRPKS product are individually reoxidized to β-ketones
by short-chain dehydrogenase/reductase enzymes, which enabled intramolecular
aldol condensation and aromatization. Our work expands the chemical
space of natural products accessible through HRPKS pathways.